Altered CSF Orexin and α-Synuclein Levels in Dementia Patients.
(2012) In Journal of Alzheimer's Disease 29(1). p.125-132- Abstract
- Neurodegenerative dementia, most frequently represented by Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), is often accompanied by altered sleeping patterns and excessive daytime sleepiness. Studies showing an association between the neuropeptide orexin and AD/DLB-related processes such as amyloid-β (Aβ)1-42 plaque formation, α-synuclein accumulation, and inflammation indicate that orexin might play a pathogenic role similar to the situation in narcolepsy. Our study of patients with AD (n = 26), DLB (n = 18), and non-demented controls (n = 24) shows a decrease in cerebrospinal fluid (CSF) orexin concentrations in DLB versus AD patients and controls. The observed differences in orexin levels were found to be specific to female... (More)
- Neurodegenerative dementia, most frequently represented by Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), is often accompanied by altered sleeping patterns and excessive daytime sleepiness. Studies showing an association between the neuropeptide orexin and AD/DLB-related processes such as amyloid-β (Aβ)1-42 plaque formation, α-synuclein accumulation, and inflammation indicate that orexin might play a pathogenic role similar to the situation in narcolepsy. Our study of patients with AD (n = 26), DLB (n = 18), and non-demented controls (n = 24) shows a decrease in cerebrospinal fluid (CSF) orexin concentrations in DLB versus AD patients and controls. The observed differences in orexin levels were found to be specific to female DLB patients. We also show that the female DLB patients exclusively displayed lower levels of α-synuclein compared to AD patients and controls. Orexin was linked to α-synuclein and total-tau in female non-demented controls whereas associations between orexin and Aβ1-42 concentrations were absent in all groups regardless of gender. Thus, the proposed links between orexin, Aβ, and α-synuclein pathology could not be monitored in CSF protein concentrations. Interestingly, α-synuclein was strongly correlated to the CSF levels of total-tau in all groups, suggesting α-synuclein to be an unspecific marker of neurodegeneration. We conclude that lower levels of CSF orexin are specific to DLB versus AD and appear unrelated to Aβ1-42 and α-synuclein levels in AD and DLB. Alterations in CSF orexin and α-synuclein levels may be related to gender which warrants further investigation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2273457
- author
- Wennström, Malin LU ; Londos, Elisabet LU ; Minthon, Lennart LU and Nielsen, Henrietta LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- bodies, orexin, biomarker, dementia with Lewy, Alzheimer's disease, Alpha-synuclein
- in
- Journal of Alzheimer's Disease
- volume
- 29
- issue
- 1
- pages
- 125 - 132
- publisher
- IOS Press
- external identifiers
-
- wos:000301139000011
- pmid:22207004
- scopus:84858136734
- pmid:22207004
- ISSN
- 1387-2877
- DOI
- 10.3233/JAD-2012-111655
- language
- English
- LU publication?
- yes
- id
- db0140b3-22f3-4833-87c7-420799f842c7 (old id 2273457)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22207004?dopt=Abstract
- date added to LUP
- 2016-04-01 10:06:27
- date last changed
- 2022-02-24 22:22:09
@article{db0140b3-22f3-4833-87c7-420799f842c7,
abstract = {{Neurodegenerative dementia, most frequently represented by Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), is often accompanied by altered sleeping patterns and excessive daytime sleepiness. Studies showing an association between the neuropeptide orexin and AD/DLB-related processes such as amyloid-β (Aβ)1-42 plaque formation, α-synuclein accumulation, and inflammation indicate that orexin might play a pathogenic role similar to the situation in narcolepsy. Our study of patients with AD (n = 26), DLB (n = 18), and non-demented controls (n = 24) shows a decrease in cerebrospinal fluid (CSF) orexin concentrations in DLB versus AD patients and controls. The observed differences in orexin levels were found to be specific to female DLB patients. We also show that the female DLB patients exclusively displayed lower levels of α-synuclein compared to AD patients and controls. Orexin was linked to α-synuclein and total-tau in female non-demented controls whereas associations between orexin and Aβ1-42 concentrations were absent in all groups regardless of gender. Thus, the proposed links between orexin, Aβ, and α-synuclein pathology could not be monitored in CSF protein concentrations. Interestingly, α-synuclein was strongly correlated to the CSF levels of total-tau in all groups, suggesting α-synuclein to be an unspecific marker of neurodegeneration. We conclude that lower levels of CSF orexin are specific to DLB versus AD and appear unrelated to Aβ1-42 and α-synuclein levels in AD and DLB. Alterations in CSF orexin and α-synuclein levels may be related to gender which warrants further investigation.}},
author = {{Wennström, Malin and Londos, Elisabet and Minthon, Lennart and Nielsen, Henrietta}},
issn = {{1387-2877}},
keywords = {{bodies; orexin; biomarker; dementia with Lewy; Alzheimer's disease; Alpha-synuclein}},
language = {{eng}},
number = {{1}},
pages = {{125--132}},
publisher = {{IOS Press}},
series = {{Journal of Alzheimer's Disease}},
title = {{Altered CSF Orexin and α-Synuclein Levels in Dementia Patients.}},
url = {{http://dx.doi.org/10.3233/JAD-2012-111655}},
doi = {{10.3233/JAD-2012-111655}},
volume = {{29}},
year = {{2012}},
}